Fluid sample concentrator

Abstract

Techniques for concentrating analytes in fluid samples are described. An example method performed by a concentrator includes receiving a fluid sample; concentrating an analyte in the fluid sample by extracting water from the fluid sample; and based on concentrating the analyte in the fluid sample, outputting the fluid sample. The analyte is concentrated by extracting the water through a membrane and into a solution including at least one solute at a concentration that is greater than a concentration of at least one solute in the fluid sample, diameters of pores extending through the membrane being shorter than a diameter of the analyte and shorter than a diameter of the at least one solute.

What is claimed is: 
     
         1 . A system for detecting an analyte in a urine sample, the system comprising:
 a concentrator comprising:
 a container; 
 a solution disposed in the container comprising at least one polymer at a concentration that is greater than a concentration of at least one solute in the urine sample, the at least one solute comprising the analyte; 
 a membrane disposed inside of the container, the solution being disposed between the membrane and a sidewall of the container, wherein diameters of pores extending through the membrane are shorter than a diameter of the analyte and shorter than a diameter of the at least one polymer; 
 a sample chamber disposed in the container and configured to receive the urine sample, the membrane being disposed between the sample chamber and the solution, the solution being configured to generate a concentrated urine sample by passively removing water from the urine sample through the membrane when the urine sample is disposed in the sample chamber; 
 a hydrophobic membrane disposed between the sample chamber and an outer environment, the hydrophobic membrane being permeable to air and impermeable to the urine sample; and 
 a diagnostic assay comprising:
 a porous substrate configured to move the concentrated urine sample via capillary action; 
 a first antibody that specifically binds to the analyte, the first antibody being bound to a tag that emits a detection signal; and 
 a second antibody that specifically binds to the analyte, the second antibody being bound to the porous substrate. 
 
   
     
     
         2 . The system of  claim 1 , wherein the at least one solute in the solution comprises: polyethylene glycol (PEG) 1500 at a concentration of 2.0 grams per milliliter (g/mL). 
     
     
         3 . The system of  claim 1 , wherein the solution is configured to generate the concentrated urine sample in 10 to 60 minutes after the urine sample is initially disposed in the sample chamber, and
 wherein the concentration of the analyte in the concentrated urine sample is at least 100 times greater than the concentration of the analyte in the urine sample.   
     
     
         4 . A concentrator, comprising:
 a container;   a solution disposed in the container comprising at least one first solute at a concentration that is greater than a concentration of at least one second solute in a fluid sample, the fluid sample comprising an analyte; and   a membrane disposed inside of the container, the solution being disposed between the membrane and a sidewall of the container, diameters of pores extending through the membrane being shorter than a diameter of the analyte and shorter than a diameter of the at least one first solute.   
     
     
         5 . The concentrator of  claim 4 , wherein the sidewall of the container is cylindrical. 
     
     
         6 . The concentrator of  claim 4 , wherein the solution comprises at least one of water or a hydrophilic solvent. 
     
     
         7 . The concentrator of  claim 4 , wherein the concentration of the at least one first solute in the solution is greater than or equal to 0.2 grams per milliliter (g/mL). 
     
     
         8 . The concentrator of  claim 4 , wherein the concentration of the at least one first solute in the solution is less than or equal to 3 g/mL. 
     
     
         9 . The concentrator of  claim 4 , wherein a molecular weight of the at least one first solute is in a range of 1,500 to 1,000,000 Daltons (Da). 
     
     
         10 . The concentrator of  claim 4 , wherein the at least one first solute comprises at least one of a polymer, a detergent, a surfactant, or a micelle. 
     
     
         11 . The concentrator of  claim 4 , wherein the at least one first solute comprises at least one of polyethylene glycol (PEG), polystyrene sulfonate (PSS), polyacrylic acid (PAA), polyethyleneimine (PEI), pectin, or sodium dodecyl sulfate (SDS). 
     
     
         12 . The concentrator of  claim 4 , wherein the analyte comprises at least one of tuberculosis antigen lipoarabinomannan (LAM), human immunodeficiency virus (HIV), human growth hormone (hGH), cell-free DNA, human chorionic gonadotropin (hCG), SARS-CoV-2 nucleocapsid (N) protein, an exosome, ribonucleic acid (RNA), a polysaccharide, a bacterium, or a virus. 
     
     
         13 . The concentrator of  claim 4 , wherein the analyte comprises human chorionic gonadotropin (hCG) or SARS-CoV-2 N protein. 
     
     
         14 . The concentrator of  claim 4 , wherein the fluid sample comprises at least one of urine, saliva, or a nasopharyngeal swab. 
     
     
         15 . The concentrator of  claim 4 , wherein the diameters of the pores are within a range of 2 nanometers (nm) to 100 nm. 
     
     
         16 . The concentrator of  claim 4 , wherein the membrane comprises cellulose. 
     
     
         17 . The concentrator of  claim 4 , wherein the membrane is a right prism. 
     
     
         18 . The concentrator of  claim 17 , wherein a cross-section of the right prism comprises at least one of a circle, a concave polygon, or a convex polygon. 
     
     
         19 . The concentrator of  claim 4 , further comprising:
 an insert disposed in the container and spaced apart from the membrane by a distance, the membrane being disposed between the insert and the solution.   
     
     
         20 . The concentrator of  claim 19 , wherein the distance is in a range of 0.5 millimeters (mm) to 20 mm. 
     
     
         21 . The concentrator of  claim 19 , wherein a ratio between a surface area of the membrane and a volume of a space disposed between the insert and the membrane is in a range of 1 to 10 centimeters squared per milliliter (cm 2 /mL). 
     
     
         22 . The concentrator of  claim 4 , further comprising:
 a collection cap removably coupled to the container and defining a collection volume that is fluidly coupled to a space disposed inside of the container, the membrane being disposed between the solution and the space disposed inside of the container.   
     
     
         23 . The concentrator of  claim 4 , further comprising:
 a funnel configured to direct the fluid sample into a space disposed inside of the container, the membrane being disposed between the space and a sidewall of the container.   
     
     
         24 . The concentrator of  claim 4 , wherein the membrane is disposed between a sample chamber and the solution and the solution is disposed in a solution chamber that is disposed between the membrane and the sidewall of the container, and
 wherein the concentrator further comprises a hydrophobic membrane disposed between the sample chamber and an exterior space outside of the concentrator and disposed between the solution chamber and the exterior space, the hydrophobic membrane being permeable to air and impermeable to the fluid sample.   
     
     
         25 . A system comprising:
 the concentrator of  claim 4 ; and   a diagnostic assay configured to detect the presence of the analyte in a sample, a lower detection limit of the diagnostic assay being greater than the concentration of the analyte in the fluid sample.   
     
     
         26 . The system of  claim 25 , wherein the diagnostic assay comprises a lateral flow assay. 
     
     
         27 . A method performed by a concentrator, the method comprising:
 receiving a fluid sample;   concentrating an analyte in the fluid sample by extracting water from the fluid sample through a membrane and into a solution comprising at least one first solute at a concentration that is greater than a concentration of at least one second solute in the fluid sample, diameters of pores extending through the membrane being shorter than a diameter of an analyte in the fluid sample, shorter than a diameter of the at least one first solute, and shorter than a diameter of the at least one second solute; and   based on concentrating the analyte in the fluid sample, outputting the fluid sample.   
     
     
         28 . The method of  claim 27 , wherein the concentration of the at least one first solute in the solution is greater than or equal to 0.2 grams per milliliter (g/mL). 
     
     
         29 . The method of  claim 27 , wherein the concentration of the at least one first solute in the solution is less than or equal to 3 g/mL. 
     
     
         30 . The method of  claim 27 , wherein a molecular weight of the at least one first solute is in a range of 1,500 to 1,000,000 Daltons (Da). 
     
     
         31 . The method of  claim 27 , wherein the at least one first solute comprises at least one of polyethylene glycol (PEG), polystyrene sulfonate (PSS), polyacrylic acid (PAA), polyethyleneimine (PEI), pectin, or sodium dodecyl sulfate (SDS). 
     
     
         32 . The method of  claim 27 , wherein the analyte comprises at least one of tuberculosis antigen lipoarabinomannan (LAM), human immunodeficiency virus (HIV), human growth hormone (hGH), cell-free DNA, human chorionic gonadotropin (hCG), SARS-CoV-2 nucleocapsid (N) protein, an exosome, ribonucleic acid (RNA), a polysaccharide, a bacterium, or a virus. 
     
     
         33 . The method of  claim 27 , wherein a ratio between a surface area of the membrane and the volume of the fluid sample is in a range of 1 to 10 centimeters squared per milliliter (cm 2 /mL). 
     
     
         34 . The method of  claim 27 , wherein the water is passively extracted from the fluid sample. 
     
     
         35 . The method of  claim 27 , wherein concentrating the analyte in the fluid sample comprises increasing the concentration of the analyte in the fluid sample by 10 to 1,000 times within 10 to 60 minutes. 
     
     
         36 . The method of  claim 27 , wherein outputting the fluid sample comprises:
 outputting the fluid sample into a collection cap.   
     
     
         37 . The method of  claim 27 , further comprising:
 receiving an insert in a sample chamber, a distance between the insert and the sample chamber being in a range of 0.5 millimeters (mm) to 20 mm   wherein the fluid sample is disposed inside of the sample chamber and between the insert and the membrane.   
     
     
         38 . The method of  claim 27 , wherein receiving the fluid sample comprises funneling the fluid sample into a sample chamber, the membrane being disposed between the sample chamber and a sidewall of the container. 
     
     
         39 . The method of  claim 27 , wherein the fluid sample comprises at least one of blood, urine, blood, saliva, serum, semen, mucus, or a nasopharyngeal swab. 
     
     
         40 . The method of  claim 39 , based on outputting the fluid sample, outputting, by a diagnostic assay, a detection signal indicative of the analyte in the fluid sample by:
 receiving a sample of the fluid sample at a porous substrate;   moving the sample into a detection region of the porous substrate;   binding a first antibody to the analyte, the first antibody being conjugated with a tag; and   binding a second antibody to the analyte, the second antibody being bound to the porous substrate,   wherein the tag outputs the detection signal.   
     
     
         41 . A concentrator, comprising:
 a membrane, diameters of pores extending through the membrane being shorter than a diameter of a target in a fluid sample; and   a solution disposed on a side of the membrane, the solution comprising at least one first solute at a concentration that is greater than a concentration of at least one second solute in the fluid sample, a diameter of the at least one first solute being greater than the diameters of the pores extending through the membrane.   
     
     
         42 . The concentrator of  claim 41 , wherein the target comprises at least one of a biopharmaceutical, a biologic, or an analyte. 
     
     
         43 . The concentrator of  claim 41 , wherein the concentrator comprises a sidewall at least partially enclosing a space, the sidewall comprising the membrane, the solution being disposed in the space.